Molecular Profile of Priapism Associated with Low Nitric Oxide Bioavailability

Justin D. La Favor, Zongming Fu, Vidya Venkatraman, Trinity J. Bivalacqua, Jennifer E. Van Eyk, Arthur L. Burnett

Research output: Contribution to journalArticlepeer-review

Abstract

Priapism is a disorder in which prolonged penile erection persists uncontrollably, potentially leading to tissue damage. Priapism commonly afflicts patient populations with severely low nitric oxide (NO) bioavailability. Because NO is a primary mediator of erection, the molecular mechanisms involved in priapism pathophysiology associated with low NO bioavailability are not well-understood. The objective of this study was to identify dysregulated molecular targets and signaling pathways in penile tissue of a mouse model of low NO bioavailability that have potential relevance to priapism. Neuronal plus endothelial NO synthase double knockout mice (NOS1/3-/-) were used as a model of low NO bioavailability. Priapic-like activity was demonstrated in the NOS1/3-/- mice relative to wild-type (WT) mice by the measurement of prolonged erections following cessation of electrical stimulation of the cavernous nerve. Penile tissue was processed and analyzed by reverse-phase liquid chromatography tandem mass spectrometry. As a result, 1279 total proteins were identified and quantified by spectral counting, 46 of which were down-regulated and 110 of which were up-regulated in NOS1/3-/- versus WT (P < 0.05). Ingenuity Pathway Analysis of differentially expressed proteins revealed increased protein kinase A and G-protein coupled receptor signaling in NOS1/3-/- penises, which represent potential mechanisms contributing to priapism for secondary to low NO bioavailability.

Original languageEnglish (US)
Pages (from-to)1031-1040
Number of pages10
JournalJournal of proteome research
Volume17
Issue number3
DOIs
StatePublished - Mar 2 2018

Keywords

  • GPCR
  • PKA
  • erectile
  • mass spectrometry
  • nitric oxide
  • penis
  • priapism
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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